In a 25-year-old man with weight loss, abdominal pain, bloody stools, a positive fecal occult blood test, and a family history of similar gastrointestinal symptoms, what is the most likely diagnosis?

Most Likely Diagnosis: Crohn Disease

In a 25-year-old man presenting with weight loss, abdominal pain, bloody stools, positive fecal occult blood test, and a family history of similar gastrointestinal symptoms, Crohn disease is the most likely diagnosis. 1, 2

Clinical Reasoning

Age and Presentation Pattern

• Crohn disease typically manifests between ages 15-30 years, making this patient's age highly characteristic 2, 3
• The triad of weight loss, abdominal pain, and bloody stools strongly suggests inflammatory bowel disease rather than functional disorders 1, 4
• Weight loss correlates with greater disease severity in Crohn disease and is more prominent than in ulcerative colitis 5, 2

Family History as a Discriminating Factor

• The presence of relatives with similar symptoms is a critical diagnostic clue 6
• First-degree relatives of Crohn disease patients have a 4-fold increased risk, with elevated risk extending to second- and third-degree relatives 6
• This familial clustering pattern is characteristic of inflammatory bowel disease, particularly Crohn disease 2, 3

Distinguishing from Other Options

Why Not Ulcerative Colitis (Option C)?

• While ulcerative colitis can present with bloody diarrhea and abdominal pain, the prominent weight loss and systemic symptoms favor Crohn disease 1, 5
• Ulcerative colitis typically presents with more prominent rectal bleeding, urgency, and tenesmus rather than weight loss as a primary feature 1, 5
• The unremarkable abdominal examination makes extensive colonic disease (typical of UC) less likely 6

Why Not Familial Adenomatous Polyposis (Option B)?

• FAP typically presents with asymptomatic polyps discovered on screening or with rectal bleeding in older adolescents/young adults 6
• Weight loss and abdominal pain are not characteristic presenting features of FAP 6
• FAP does not typically cause the systemic inflammatory symptoms seen here 6

Why Not Peutz-Jeghers Syndrome (Option A)?

• Peutz-Jeghers syndrome presents with hamartomatous polyps and mucocutaneous pigmentation 6
• Bleeding from Peutz-Jeghers is typically occult or from intussusception, not the inflammatory pattern described 6
• The prominent weight loss and inflammatory symptoms are not characteristic 6

Diagnostic Approach

Initial Laboratory Assessment

• Obtain complete blood count to assess for anemia and inflammatory changes 1, 4
• Measure ESR or CRP, though 15-20% of active Crohn disease patients may have normal inflammatory markers 1, 5
• Check serum albumin and nutritional markers, as hypoalbuminemia indicates severe disease 5, 7
• Measure fecal calprotectin: levels >250 μg/g strongly correlate with active inflammation 1, 8

Stool Studies

• Perform comprehensive stool cultures for entero-invasive bacterial infections 6
• Test for Clostridium difficile toxin 6, 1
• Consider testing for parasites if travel history is present 6

Definitive Diagnosis

• Colonoscopy with ileoscopy and biopsies is the gold standard for confirming Crohn disease 4, 7
• Look for skip lesions, longitudinal ulcers, aphthous ulcers, and cobblestoning—all characteristic of Crohn disease 6, 2
• CT or MR enterography should follow to assess small bowel involvement and complications (strictures, fistulae, abscesses) 6, 3

Critical Pitfalls to Avoid

• Do not assume normal inflammatory markers exclude Crohn disease: Up to 15-20% of patients with active disease have normal CRP 1, 5
• Do not overlook infectious triggers: Always exclude C. difficile and other enteric pathogens before diagnosing IBD 6, 1
• Do not delay endoscopy based on age: Young patients with alarm features (weight loss, anemia, bloody stools) require prompt colonoscopy within 30 days 1
• Do not miss perianal disease: Perform careful perianal inspection, as fistulae and abscesses are common in Crohn disease and help distinguish it from ulcerative colitis 6, 2, 4